scholarly journals 1288. Evaluation of Predictors for Clinical Success in Patients Treated with Eravacycline for Various Infections

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S733-S733
Author(s):  
Sara Alosaimy ◽  
Taylor Morrisette ◽  
Abdalhamid M Lagnf ◽  
Kyle Molina ◽  
Jeannette Bouchard ◽  
...  
Keyword(s):  
Success Factors ◽  
Clinical Success ◽  
Panel Member ◽  
The United States ◽  
Surgical Interventions ◽  
Comorbidity Scores ◽  
Infectious Diseases Consultation ◽  
La Jolla ◽  
Infection Recurrence ◽  
Research Grant

Abstract Background Eravacycline (ERV) is approved in the United States (US) for the treatment of complicated intra-abdominal infections in adults. We aimed to evaluate the independent predictors of clinical success in patients treated with ERV for various infections. Methods Multicenter, retrospective, observational study conducted from September, 2018 to April, 2021. We included adults treated with ERV for ≥ 72hours. Clinical success was defined as 30-day survival, lack of 30-day infection-recurrence, and resolution of infection signs/symptoms. All outcomes were measured from ERV initiation. Multivariable logistic regression (MLR) was performed to identify independent predictors of clinical success. Clinically relevant variables were selected for model entry based on bivariate comparisons (P< 0.2) in a backward fashion. Results We included 223 patients from 16 medical centers in 13 geographically unique states. The median (IQR) age was 61 (50-69) years, 57% were male and 62% were Caucasian. Median (IQR) APACHE II, and Charlson Comorbidity scores were 15 (10-21), and 3 (1-5), respectively. Sources of infection were primarily intra-abdominal (27%) and respiratory (27%). Common pathogens included Acinetobacter baumannii (21%) and those of the Enterobacterales order (36%). Infectious diseases consultation and surgical interventions were obtained in 93.7% and 52% respectively. Clinical success occurred in 64%, specifically 30-day survival in 78%, absence of 30-day infection-recurrence in 93%, and 74% experienced resolution of infection signs/symptoms. Since characteristics and outcomes were similar among various pathogens, MLR was conducted using the overall cohort. Skin as a source and combination therapy with ERV were independently associated with higher clinical success: odds ratio 3.3 [CI 1.1-10.2] and 2.9 [1.4-5.9], respectively. Whereas, ICU admission at culture time and undergoing surgery within 30 days of culture were independently associated with reduced odds of clinical success: 0.4 [0.17-0.80] and 0.3 [0.11-0.63] respectively. Conclusion Although most ERV treated patients experienced clinical success, factors independently associated with higher clinical success are crucial to consider for optimum antibiotic selection. Disclosures Kimberly C. Claeys, PharmD, GenMark (Speaker’s Bureau) Madeline King, PharmD, tetraphase (Speaker’s Bureau) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Bruce M. Jones, PharmD, BCPS, Abbvie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)La Jolla (Speaker’s Bureau)Melinta (Consultant)Merck (Consultant)Paratek (Consultant, Speaker’s Bureau) Susan L. Davis, PharmD, Nothing to disclose Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

scholarly journals 1577. Real-World, Multicenter Experience with Eravacycline for Various Infections

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S787-S787
Author(s):  
Sara Alosaimy ◽  
Abdalhamid M Lagnf ◽  
Kyle Molina ◽  
Madeline King ◽  
Benjamin Pullinger ◽  
...  
Keyword(s):  
Real World ◽  
The United States ◽  
Real World Data ◽  
Clinical Safety ◽  
Surgical Interventions ◽  
Start Date ◽  
Comorbidity Scores ◽  
Secondary Outcomes ◽  
Infectious Diseases Consultation ◽  
Infection Recurrence

Abstract Background Eravacycline (ERV) is Food and Drug Administration approved in patients for the treatment of adults complicated intra-abdominal infections in 2018. Real-world data regarding the indications for ERV use are is limited. We evaluated the clinical/safety outcomes of patients treated with ERV in FDA and non-FDA approved indications. Methods Multicenter, retrospective, observational study from September 2018 to June 2020. Adult patients treated with ERV for ³ 72 hours were included. The primary outcome was 30-day survival. Secondary outcomes included a lack of 30-day infection-recurrence, resolution of signs/symptoms of infection and safety. All outcomes were measured from ERV start date. Results Overall, 108 patients were included from 12 geographically-distinct medical centers across the United States. The median(IQR) age was 60(52-67) years and 60% were male. Median(IQR) APACHE II and Charlson Comorbidity scores were 15(11-21) and 3 (2-6), respectively. The most common sources of infection were intra-abdominal (32%), and respiratory (24%). Common pathogens included Acinetobacter baumannii (19%), Klebsiella pneumoniae and Enterococcus faecium (16%). Infectious diseases consultation was obtained in 98%, and surgical interventions in 51% of cases. Patients often received active therapy prior to ERV(40%). Median(IQR) ERV therapy duration was 7.7(4.4-14.0) days. Among cases with documented cultures, ERV was initiated within a median(IQR) of 4.8(2.5-9.9) days. Combination therapy ³ 48 hours was given in 45%. The primary endpoint was achieved in 79%(85/108). Of patients who died(n=23), 57% were on monotherapy, 39% were critically ill, 39% had intra-abdominal as a source, and 30% had positive blood cultures. For secondary outcomes, 94%(102/108) lacked 30-day infection-recurrence and 74%(80/108) resolved signs/symptoms of infection. ERV was selected primarily for consolidation of the regimen(40%). Eight patients experienced a probable ERV-related adverse event, mainly gastrointestinal(87.5%) and none experienced clostridium difficile. Conclusion 30-day survival was achieved in the majority of patients treated with ERV. Studies with longer follow-up are required to confirm these findings. Disclosures Madeline King, PharmD, Tetraphase (Speaker’s Bureau) Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Michael J. Rybak, PharmD, MPH, PhD, Paratek (Grant/Research Support)

scholarly journals 1373. Vaccine Effectiveness and Pneumococcal Serotypes in Pediatric Otitis Media in the Era of Routine 13-valent Pneumococcal Vaccination in the United States

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S696-S697
Author(s):  
Kristina G Hulten ◽  
William Barson ◽  
P Ling Lin ◽  
John S Bradley ◽  
Timothy R Peters ◽  
...  
Keyword(s):  
Otitis Media ◽  
Acute Otitis Media ◽  
Pneumococcal Vaccination ◽  
Panel Member ◽  
The United States ◽  
Vaccine Effectiveness ◽  
Pneumococcal Serotypes ◽  
Research Support ◽  
Review Panel ◽  
Research Grant

Abstract Background Pneumococcal acute otitis media (AOM) in children due to vaccine related serotypes (St) declined after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). Methods Patients < 18 years with pneumococcal OM isolates from 2014-2019 from the U S Pediatric Multicenter Pneumococcal Surveillance Group were analyzed for demographics, immunization status, antimicrobial susceptibility and St distribution. p< 0.05 was considered statistically significant. Vaccine effectiveness (VE) was calculated using a standard formula: 1-([PCV13St vaccinated (≥3 PCV13 doses) x Non-PCV13St unvaccinated (0-1 PCV13 doses)]/[PCV13St unvaccinated x Non-PCV13St vaccinated]) Results 646 patients were identified. Patients with PCV13 St were older compared to patients with non-PCV13 serotypes (3.3 vs 1.5 median years, p< 0.0001). Most isolates were from spontaneous drainage (71.4 %) and PE tube placements (26.9%). 36 different Sts were identified; 83.4% of isolates were non-PCV13 Sts; 35B represented 18.3% of all isolates. St 19A decreased over time (p=0.0003). 14% of isolates had penicillin MIC ≥2 µg/ml and 2.4% had ceftriaxone MIC >1 µg/ml. (Figure) 633 patients had known vaccine status. VE was 86.4% (Table). Table. Conclusion Non-PCV13 Sts caused most pneumococcal OM. St35B was the most common St. St 19A decreased as a cause of otitis. In this study the VE of≥3 PCV13 doses was 86% for pneumococcal OM. Disclosures Tina Q. Tan, MD, Pfizer (Grant/Research Support, Other Financial or Material Support, Chair, DMSB for PCV20 vaccine) Pia S. Pannaraj, MD, MPH, AstraZeneca (Grant/Research Support)Pfizer (Grant/Research Support)Sanofi Pasteur (Advisor or Review Panel member) Sheldon L. Kaplan, MD, Allergan (Research Grant or Support)Pfizer (Grant/Research Support)

scholarly journals 1082. Real-World Experience with Omadacycline for Nontuberculous Mycobacterial Infections: A Multicenter Evaluation

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S632-S633
Author(s):  
Taylor Morrisette ◽  
Sara Alosaimy ◽  
Abdalhamid M Lagnf ◽  
Julie V Philley ◽  
Carly Sigler ◽  
...  
Keyword(s):  
Real World ◽  
Randomized Clinical Trials ◽  
Clinical Success ◽  
Panel Member ◽  
Mycobacterium Abscessus ◽  
Primary Objective ◽  
Real World Evidence ◽  
Gastrointestinal Distress ◽  
Research Grant

Abstract Background Nontuberculous mycobacteria (NTM) are resistant to numerous antibiotics and lead to significant morbidity and mortality. Omadacycline (OMC) is an aminomethylcycline antibiotic that is Food and Drug Administration-approved for acute bacterial skin and skin structure infections and community-acquired bacterial pneumonia. Furthermore, OMC has shown in vitro activity against NTM. Given that real-world evidence is lacking, our primary objective was to evaluate the clinical success and tolerability of OMC when used for a variety of NTM infections. Methods This was a multicenter, retrospective, observational study conducted from January 2020 to June 2021. We included all patients ≥ 18 years of age that received OMC of any indication for Mycobacterium spp. The primary outcome was clinical success, defined as a lack of all-cause mortality, lack of persistence or re-emergence of infection during or after therapy, and lack of alteration of OMC. Incidence of adverse effects potentially attributable to OMC and reasons for OMC utilization were also analyzed. Results A total of 31 patients were included from 12 geographically distinct academic health systems (median age: 57 (IQR, 45-63) years; 45% male; 81% Caucasian). The majority of isolated pathogens were Mycobacterium abscessus complex (84%) and of those with subspeciation performed (54%), the majority (86%) were subsp. abscessus. The primary infections were of pulmonary origin (67%) and the median (IQR) duration of OMC therapy was 5.3 (3.2-9.4) months. Most isolates did not have OMC susceptibility conducted (87%), while the majority did for tigecycline (90%). Clinical success was reported in 81% of the population. Most patients were on combination antimicrobial therapy, and 39% of patients reported an adverse effect while on OMC (58% gastrointestinal distress). The majority of patients were prescribed OMC due to ease of administration (61%) and antimicrobial resistance to previous antibiotics (42%). Conclusion OMC may be a potential option for the therapy of NTM infections. Prospective, randomized clinical trials are needed to confirm our preliminary findings. Disclosures Julie V. Philley, MD, Paratek Pharmaceuticals (Advisor or Review Panel member)Paratek Pharmaceuticals, Inc. (Consultant) Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Michael J. Rybak, PharmD, MPH, PhD, Paratek Pharmaceuticals (Research Grant or Support)

scholarly journals 1084. Comparative Outcomes Among Patients Receiving Varying Daptomycin Dosing Regimens in Hemodialysis

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S633-S634
Author(s):  
Tyler Maxwell ◽  
James E Orban ◽  
Wesley D Kufel ◽  
Christopher Destache ◽  
Karen S Williams ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Small Sample Size ◽  
Panel Member ◽  
The United States ◽  
Small Sample ◽  
Pharmacokinetic Studies ◽  
Research Support ◽  
Review Panel ◽  
Dosing Regimens ◽  
Research Grant

Abstract Background Daptomycin (DAP) has become an appealing treatment option for gram-positive infections, which are common in patients receiving hemodialysis (HD), due to frequent access and manipulation. The approved DAP dosing of 4 to 6 mg/kg every 48 hours (q48h) quickly becomes desynchronized from the patient’s HD schedule and requires the burden of additional IV access. Previous pharmacokinetic studies have suggested that DAP can be dosed three-times weekly following HD, but no studies have evaluated clinical outcomes of this regimen. Methods This was a multi-center, retrospective cohort study across 6 hospitals in the United States. Adult, nonpregnant patients who received HD and DAP between 2015 and 2020 were screened for inclusion. Electronic medical records were reviewed for relevant study data. The primary outcome was clinical and microbiological outcomes among patients who received DAP thrice weekly versus q48h dosing. Microbiological Failure was defined as positive cultures after 7 days and further study definitions are included under Table 3. Results Baseline characteristics are summarized in Table 1. Length of stay was similar between both groups at a median of 25 days and patients had a median QPitt score of 0 on admission. The average DAP dose used was 7 mg/kg and 7mg-7mg-9mg on HD days in the q48h dosing and thrice weekly dosing regimens, respectively. The majority of patients had bacteremia and the most commonly isolated bacteria was methicillin-resistant Staphylococcus aureus. No differences in clinical outcomes were observed (p=0.87). Microbiological failure was higher among patients who received DAP thrice weekly compared to q48h dosing (69.2% vs 34.8%, p=0.047). Conclusion DAP dosed thrice weekly on HD days offers similar clinical resolution compared to q48h dosing. While the thrice weekly dosing regimen did have a significantly higher rate of microbiological failure, the analysis was limited by a small sample size. As this is a retrospective analysis not accounting for confounding variables, additional prospective studies are warranted to confirm these findings. Disclosures Wesley D. Kufel, PharmD, Melinta (Research Grant or Support)Merck (Research Grant or Support)Theratechnologies, Inc. (Advisor or Review Panel member) P. Brandon Bookstaver, Pharm D, ALK Abello, Inc. (Grant/Research Support, Advisor or Review Panel member)Biomerieux (Speaker's Bureau)Kedrion Biopharma (Grant/Research Support, Advisor or Review Panel member)

scholarly journals 57. Evaluating the Utility of a Penicillin Allergy Reconciliation Program within an Infectious Diseases Consult Population in a Community Health System

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S49-S50
Author(s):  
Bruce M Jones ◽  
Emily Plauche ◽  
Susan E Smith ◽  
Christopher M Bland
Keyword(s):  
Infectious Diseases ◽  
Health System ◽  
Community Health ◽  
Intervention Program ◽  
Primary Outcome ◽  
Panel Member ◽  
Penicillin Allergy ◽  
Secondary Outcome ◽  
Research Support ◽  
Research Grant

Abstract Background Penicillin allergy reconciliation is an important aspect of antimicrobial stewardship with ~10% of the population reporting a penicillin allergy. Our facility utilizes a Penicillin Allergy Reconciliation Program (PARP) led by an Infectious Diseases (ID) Pharmacist and pharmacy students to identify patients with penicillin allergies to reconcile and intervene when necessary. Information is collected by interview, electronic medical record (EMR) review, prescription outpatient fill history. This study evaluated reconciliations with and without a PARP in patients in a community health system. Methods This was a retrospective study that compared reconciliations performed on adult patients admitted at least once in 2019 with a self-reported penicillin allergy and ID physician consult at a hospital with a PARP (Institution 1) and one without a formal evaluation and intervention program (Institution 2) within the same community health system with same ID physicians. The primary outcome was documented reconciliation of a patient’s penicillin allergy during an inpatient visit in 2019. Reconciliation was defined as an edit or clarification (updating the severity, reaction, or comments section, as well as deleting) to a patient’s penicillin allergy in the EMR. The secondary outcome evaluated the percentage of total and ID consult patients with a penicillin allergy. Results There were 245 patients who met criteria and were included in the study, 113 from Institution 1 and 132 from Institution 2. For the primary outcome, there were 82 (72.6%) reconciliations at Institution 1 and 15 (11.4%) reconciliations at Institution 2 (p < 0.001). Interventions at Institution 1 and 2 resulted in 74 EMR updates and 8 removals and 14 EMR updates and 1 removal, respectively. Reconciliation was performed on the same visit as the ID consult in 59/82 patients (72%) at Institution 1 and 11/15 patients (73.3%) at Institution 2. All reconciliations at Institution 2 were made by pharmacist (10) or nurses (5). For the secondary outcome, 10.9% of patients with an ID consult and 12.6% of all patients admitted in 2019 had a penicillin allergy (p=0.027). Conclusion A PARP led by an ID pharmacist and students was an effective method to perform penicillin allergy reconciliations, even in the presence of active ID consultation. Disclosures Bruce M. Jones, PharmD, BCPS, ALK-Abello (Research Grant or Support)Allergan/Abbvie (Speaker’s Bureau) Christopher M. Bland, PharMD, FCCP, FIDSA, BCPS, ALK Abello, Inc. (Grant/Research Support)Biomerieux (Consultant)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member, Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

scholarly journals 1066. Immune Escape Mutant Detection Using Commercially Available Methods for Hepatitis B Surface Antigen Serological Testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S562-S562
Author(s):  
Robert Gish ◽  
Vincent Streva
Keyword(s):  
Hepatitis B ◽  
Immune Escape ◽  
Hepatitis B Surface Antigen ◽  
Panel Member ◽  
The United States ◽  
Hbv Infection ◽  
Hepatitis B Vaccination ◽  
Review Panel ◽  
B Virus ◽  
Escape Mutants

Abstract Background Although overall infection rates of Hepatitis B virus (HBV) in the United States (US) remain stable, as many as 2.2 million persons are still chronically infected with Hepatitis B Virus (HBV)1. Persons who inject drugs (PWID) are at a higher risk of HBV infection and since 2009 three states (KY, TN, WV) have reported up to a 114% increase in cases of acute HBV infection due to higher infection rates among a non-Hispanic white populations (30–39 years), and injection drug users2. Hepatitis B vaccination is recommended as primary prevention for adults who are at increased risk for HBV infection, including PWID. However, data from the National Health Interview Survey indicate that hepatitis B vaccination coverage is low among adults in the general population3, and it is likely to be lower among injection drug users. Hepatitis B Surface Antigen (HBsAg) is the first serological marker to appear after HBV exposure and infection; this marker is included in the recommended panel for acute hepatitis diagnosis and accurate detection is necessary for early and accurate diagnosis. Serological testing challenges exist for HBsAg due to the high degree of genetic variability which can further be exacerbated by endogenous and exogenous pressures. The immuno-dominant region may have one or more mutations described as immune escape mutations which can decrease or abrogate HBsAg binding to antibodies used in immunoassays. Although the prevalence of these mutations is not well documented in the United States, international studies have shown that up to 79% of HBV-reactivated patients (vs 3.1% of control patients; p< 0.001) carry HBsAg mutations localized in immune-active HBsAg regions4. Methods A study was conducted using a panel of 10 unique recombinant HBsAg immune escape mutants. Panel members were tested by commercially available HBsAg serological immunoassays. Results It was found that although commercially available HBsAg immunoassays are the primary diagnostic tool for HBV diagnosis, not all HBsAg immune escape mutants are detected, with some method detecting as few as 5 out of 10 of these mutant samples. Figure 1 Conclusion Improvement is needed in commercially available methods for the accurate detection of HBsAg. Disclosures Robert Gish, MD, Abbott (Consultant)AbbVie (Consultant, Advisor or Review Panel member, Speaker’s Bureau)Access Biologicals (Consultant)Antios (Consultant)Arrowhead (Consultant)Bayer (Consultant, Speaker’s Bureau)Bristol Myers (Consultant, Speaker’s Bureau)Dova (Consultant, Speaker’s Bureau)Dynavax (Consultant)Eiger (Consultant, Advisor or Review Panel member)Eisai (Consultant, Speaker’s Bureau)Enyo (Consultant)eStudySite (Consultant, Advisor or Review Panel member)Exelixis (Consultant)Fujifilm/Wako (Consultant)Genentech (Consultant)Genlantis (Consultant)Gilead (Consultant, Advisor or Review Panel member, Speaker’s Bureau)GLG (Consultant)HepaTX (Consultant, Advisor or Review Panel member)HepQuant (Consultant, Advisor or Review Panel member)Intercept (Consultant, Speaker’s Bureau)Ionis (Consultant)Janssen (Consultant)Laboratory for Advanced Medicine (Consultant)Lilly (Consultant)Merck (Consultant)Salix (Consultant, Speaker’s Bureau)Shionogi (Consultant, Speaker’s Bureau)Viking (Consultant)

scholarly journals 1608. Efficacy of Ceftolozane/Tazobactam for Multidrug-Resistant Gram-Negative Infections in Multiple Urban Hospitals

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S798-S799
Author(s):  
Nicolo Cabrera ◽  
Truc T Tran ◽  
Travis J Carlson ◽  
Faris Alnezary ◽  
William R Miller ◽  
...  
Keyword(s):  
Research Study ◽  
Clinical Success ◽  
Significant Proportion ◽  
Scientific Research ◽  
Panel Member ◽  
Multidrug Resistant ◽  
Outcome Data ◽  
Research Support ◽  
Gram Negative ◽  
Study Investigator

Abstract Background Ceftolozane/tazobactam (C/T) is a novel cephalosporin/beta-lactamase inhibitor combination developed for use against multidrug-resistant (MDR) Gram-negative infections, particularly Pseudomonas aeruginosa (PA). C/T is approved for complicated urinary tract and intraabdominal infections as well as hospital-acquired/ventilator-associated bacterial pneumonias. However, comprehensive clinical characterization of patients treated with C/T in non-FDA-approved indications is limited. Methods Patients ≥18 years who received C/T for ≥48 hours while hospitalized in 9 acute care centers in Houston, TX from January 2016 through September 2018 were included. Demographic, microbiologic, treatment and clinical outcome data were retrospectively collected by chart review. In patients who received multiple inpatient courses of C/T, only the first course with C/T was assessed. Results 210 patients met inclusion criteria: 58% were non-white, 35% were female and 13% were immunocompromised. Median age was 61 years (IQR, 48 to 69). Median Charlson comorbidity index was 5 (IQR, 2 to 6). At the onset of the index episode, a significant proportion of patients required intensive care unit admission (44%), mechanical ventilation (37%) and pressor support (22%). Respiratory sources were the most common (50%) followed by urine (15%). Positive cultures were documented in 93% of the cases and PA was found in 86%. Majority (95%) of PA which were MDR. C/T use was guided by susceptibility testing of the index isolate in ca. 52%. In 5.7% of cases, C/T was used to escalate therapy without any documented C/T-susceptible organism. Half (51%) of the cohort received initial dosing appropriate for renal function while 36% receiving a lower than recommended dose. Clinical success (i.e., recovery from infection-related signs and symptoms) occured in 77%. The in-hospital mortality rate in our cohort was 15% with 26 of 31 deaths deemed infection-related. Conclusion We report a large multicenter observational cohort that received C/T. A 77% clinical success with the use of C/T was documented. These data support the use of C/T in critically ill patients infected with MDR PA. Disclosures William R. Miller, MD, Entasis Therapeutics (Scientific Research Study Investigator)Merck (Grant/Research Support)Shionogi (Advisor or Review Panel member) Laura A. Puzniak, PhD, Merck (Employee) Cesar A. Arias, MD, MSc, PhD, FIDSA, Entasis Therapeutics (Scientific Research Study Investigator)MeMed (Scientific Research Study Investigator)Merck (Grant/Research Support)

scholarly journals 1104. Risk Factors and Outcomes of Refractory and/or Resistant Cytomegalovirus (CMV) Infection after Allogeneic Hematopoietic Stem Cell Transplantation

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S582-S583
Author(s):  
Eleni Karantoni ◽  
Yiqi Su ◽  
Anat Stern ◽  
Phaedon D Zavras ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
T Cell ◽  
Panel Member ◽  
Multivariable Model ◽  
Research Support ◽  
Review Panel ◽  
Material Support ◽  
Advisory Boards ◽  
Research Grant

Abstract Background The epidemiology of CMV end-organ disease (EOD) after Hematopoietic Cell Transplant (HCT) in the era of preemptive therapy (PET) is defined. In contrast, less data exists on refractory and/or resistant (R/R) CMV. We report on 1) the incidence; 2) risk factors and outcomes of R/R CMV by 1-year post HCT. Methods Retrospective review of 167 CMV seropositive (R+) recipients of first marrow or peripheral blood HCT from 1/2014 - 12/2017 managed by PET. Refractory CMV was defined as failure to achieve >1 log10 decrease in CMV viral load (VL) and having VL >1,000 IU/mL after ≥14 day of PET. Resistant CMV required genotypic confirmation of resistance mutation(s) in UL54 and/or UL97 genes. End organ disease (EOD) was defined by standard criteria. Patients (pts) were followed through 1-year post HCT and were categorized in two mutually exclusive groups as R/R and no R/R. Demographics, clinical characteristics and outcomes were extracted from medical records and hospital databases. Univariable and multivariable logistic models were used to identify risk factors for R/R CMV. Results Of 167 PET recipients, 91 (54.5%) received ex vivo T cell depleted (TCD) HCT; 40 (24.0%) had mismatched donor; and 26 (15.6%) had multiple myeloma. 66/167 (39.5%) pts developed refractory CMV (6 pts also had resistant CMV). Time from HCT to CMV viremia was shorter in R/R group: median (IQR) 21.5 (17.2-27.8) days compared to no R/R group: 26 (19-32) days (p=0.031). Maximum VL was higher for R/R compared to no R/R: median (IQR) 9,118 (2,849-18,456) and 868 (474-1,908), respectively (p< 0.001). In multivariable model, risk factors for R/R included TCD HCT (p< 0.0001) and higher VL at PET initiation (p=0.0002). In contrast, CMV seropositive donor (p=0.035) was protective (Figure 1). CMV EOD developed in 28.2% of R/R and 16.2% of no R/R groups (p=0.085) (Figure 2). Overall survival at 1 year was 59.1% for R/R compared to 83.1% for no R/R group (p=0.00027) (Figure 3). Figure 1. Adjusted odds ratio (OR) and 95% confidence interval (CI) from multivariable model evaluating risk factors of refractory/resistant (R/R) CMV. Figure 2. Cumulative incidence curves of CMV end-organ disease (EOD) at 1-year post HCT Figure 3. Kaplan-Meier survival curves of overall survival (OS) at 1-year post HCT Conclusion 1) Refractory and/or resistant CMV occurred in 39,5% of PET recipients. 2) T-cell depletion and higher CMV VL at PET initiation were risk factors for R/R CMV in multivariable models. 3) R/R CMV was associated with more EOD and worse overall survival. Disclosures Sergio Giralt, MD, Amgen (Advisor or Review Panel member, Research Grant or Support, Served an advisory board for Amgen, Actinuum, Celgene, Johnson & Johnson, JAZZ pharmaceutical, Takeda, Novartis, KITE, and Spectrum pharma and has received research support from Amgen, Actinuum, Celgene, Johnson & Johnson, and Miltenyi, Takeda.) Miguel-Angel Perales, MD, Abbvie (Other Financial or Material Support, Honoraria from Abbvie, Bellicum, Celgene, Bristol-Myers Squibb, Incyte, Merck, Novartis, Nektar Therapeutics, Omeros, and Takeda.)ASTCT (Other Financial or Material Support, Volunteer member of the Board of Directors of American Society for Transplantation and Cellular Therapy (ASTCT), Be The Match (National Marrow Donor Program, NMDP), and the CIBMTR Cellular Immunotherapy Data Resource (CIDR) Committee)Cidara Therapeutics (Advisor or Review Panel member, Other Financial or Material Support, Serve on DSMBs for Cidara Therapeutics, Servier and Medigene, and the scientific advisory boards of MolMed and NexImmune.)Kite/Gilead (Research Grant or Support, Other Financial or Material Support, Received research support for clinical trials from Incyte, Kite/Gilead and Miltenyi Biotec.) Genovefa Papanicolaou, MD, Chimerix (Research Grant or Support)Merck&Co (Research Grant or Support, Investigator and received funding and consulting fees from Merck, Chimerix, Shire and Astellas)

scholarly journals 1475. Impact of a Routine Infant PCV Program on the Serotype Distribution of Episodes of Invasive Pneumococcal Disease (IPD) and Non-bacteremic Pneumococcal Pneumonia in Adults

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S739-S739
Author(s):  
Allison McGeer
Keyword(s):  
Pneumococcal Pneumonia ◽  
Herd Immunity ◽  
Panel Member ◽  
Population Based ◽  
Review Panel ◽  
Vaccine Type ◽  
Bacteremic Pneumococcal Pneumonia ◽  
Type Strains ◽  
Routine Infant ◽  
Research Grant

Abstract Background Herd immunity from pediatric pneumococcal conjugate vaccine (PCV) programs has resulted in substantial reductions in IPD due to PCV serotypes (ST). We assessed whether similar changes in ST distribution occur in non-bacteremic pneumococcal pneumonia (NBPP). Methods The Toronto Invasive Bacterial Diseases Network performs population-based surveillance for IPD and hospitalized, culture-confirmed NBPP in Toronto/Peel Region, Canada (Pop 4.5M). Patient data are collected by interview/chart review; illness associated with respiratory isolates is categorized using Musher criteria. Results Since 2002, 6627 episodes of IPD, and 7323 non-bacteremic episodes with a respiratory isolate of S. pneumoniae (2180 meeting modified Musher criteria for NBPP) have occurred in adults. Distributions of vaccine-type serotypes in IPD and NBPP pre-PCV7 (2002-2004), post-PCV7 (2006-2009) and late post-PCV13 (2014-2019) are shown in the Figure. There were no significant changes in distribution of vaccine serotype groups from 2014-2019 in IPD or NBPP. From 2014-2019, serotypes included in PCV13 and PCV20 were associated with 33% and 59% of IPD cases, and 29% and 49% of NBPP cases in adults.. Figure. distribution of serotype groups included in different pneumococcal vaccines in cases of IPD and non-bacteremic pneumonia Conclusion Eight years post routine infant PCV13 implementation, PCV13 type IPD and NBPP persists in adults. The distribution of vaccine-type strains is similar in IPD and NBPP; although non-vaccine-type strains are more common in NBPP. Disclosures Allison McGeer, MD, FRCPC, GlaxoSmithKline (Advisor or Review Panel member, Research Grant or Support)Merck (Advisor or Review Panel member, Research Grant or Support)Pfizer (Research Grant or Support)

scholarly journals 652. Comparison of fosfomycin (FOF) activity and prevalence of subpopulations between Escherichia coli (EC) and Klebsiella pneumoniae (KP) during susceptibility testing

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S384-S384
Author(s):  
Jadyn C Anderson ◽  
Amanda R Krueger ◽  
Elizabeth C Smith ◽  
Morgan L Bixby ◽  
Hunter V Brigman ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Inhibitory Concentration ◽  
Panel Member ◽  
Colony Growth ◽  
The United States ◽  
Research Support ◽  
Review Panel ◽  
Agreement Rate ◽  
Future Studies ◽  
Agar Dilution

Abstract Background In the United States, interpretive criteria for FOF are established only for EC, yet those criteria are often extrapolated to KP. Recent studies have highlighted both inferior clinical outcomes after FOF treatment and difficulties in interpretation of inner colony subpopulations, the presence of which may affect clinical efficacy. We sought to compare FOF activity against EC and KP and to determine the prevalence of inner colony subpopulations following disk diffusion (DD) testing of the two species. Methods A convenience collection of 73 KP and 42 EC isolates from 3 U.S. institutions were included. Minimal inhibitory concentration (MIC) testing was performed in duplicate on separate days using agar dilution (AD) and DD as recommended by the Clinical and Laboratory Standards Institute guidelines, with application of EC susceptibility (≤ 64mg/L) breakpoints. The frequency and counts of inner colonies observed during DD testing was calculated, and colonies were subcultured for use in future studies. Results MIC50/90 values were 1/16 mg/L and 32/256 mg/L for EC and KP respectively. All EC isolates were considered susceptible and therefore categorical agreement was 100%. The majority of KP isolates were considered susceptible (83.6% with AD and 86.3% with DD) and categorical agreement between the methods was 84.9%. Inner colonies were observed during DD testing in 88.1% of EC isolates and 80.8% of KP isolates during at least one replicate, with 47.6% of EC isolates and 39.7% of KP isolates showing inner colony growth during both DD test replicates. More than 10 inner colonies were observed in 50% of EC isolates compared to 12.3% of KP isolates. Conclusion KP isolates demonstrated considerably higher FOF MIC values compared to EC, as evidenced by MIC50/90 values 4-5 dilutions higher than those for EC. The categorical agreement rate was higher among EC than KP, highlighting concerns regarding the practice of extrapolating FOF susceptibility breakpoints for EC to KP. The high frequency of inner colonies observed in DD for both species necessitates further studies to determine best practices for interpreting their relevance, fitness, and resistance in order to identify potential impacts to clinical efficacy of FOF. Disclosures Elizabeth B. Hirsch, PharmD, Merck (Grant/Research Support)Nabriva Therapeutics (Advisor or Review Panel member)

Sign in / Sign up

Export Citation Format

Share Document